基于生物信息学分析氧化石墨烯量子点刺激的小鼠骨髓间充质干细胞对多发性骨髓瘤的影响及潜在分子机制  

Impact and potential molecular mechanisms analysis of graphene oxide quantum dots stimulated mouse origin bone marrow mesenchymal stem cells on multiple myeloma based on bioinformatics analysis

作　　者：魏子媛 刘丹阳 张晓东[2] 王璐璐 李永涛[2] 沈雷 Wei Ziyuan;Liu Danyang;Zhang Xiaodong;Wang Lulu;Li Yongtao;Shen Lei(Medical Technology,Qiqihar Medical University,Qiqihar,Heilongjiang 161006,China;Department of Anatomy,Qiqihar Medical University,Qiqihar,Heilongjiang 161006,China;Heilongjiang Provincial Key Laboratory of Drug Food Homologous and Prevention and Treatment for Metabolic Diseases,Qiqihar,Heilongjiang 161006,China)

机构地区：[1]齐齐哈尔医学院,黑龙江齐齐哈尔161006 [2]齐齐哈尔医学院解剖学教研室 [3]黑龙江省药食同源资源与代谢性疾病防治重点实验室

出　　处：《齐齐哈尔医学院学报》2025年第6期501-508,共8页Journal of Qiqihar Medical University

基　　金：黑龙江省自然科学基金联合引导项目(LH2021H121)。

摘　　要：目的探讨氧化石墨烯量子点(GOQD)刺激的小鼠骨髓间充质干细胞(mBMSC)对小鼠多发性骨髓瘤发生过程的影响及其潜在分子机制。方法正常培养的mBMSC为对照组,含100μg/ml GOQD培养的mBMSC为实验组。两组均在37℃、5%CO_(2)条件下培养24 h后,转录组测序技术检测两组基因。R4.2.1的Edge R包筛选实验组的差异表达基因(GOQD-DEG);GEO数据库的GSE6980数据集获得小鼠多发性骨髓瘤差异表达基因(MM-DEG),对GOQD-DEG和MM-DEG的交集基因进行后续分析。Fgsea R包和GO.db R包对交集基因的生物过程、分子功能、KEGG信号通路进行分析;Cluster Profiler R包进行基因集富集分析(GSEA);String构建交集基因编码的蛋白质与蛋白质相互作用网络(PPI),Cytohubba v0.1 App筛选排名前10的核心蛋白,stats 4.2.1 R包和car 3.1-0 R包分析核心蛋白在多发性骨髓瘤的表达,pROC 1.18.0 R包绘制核心蛋白在小鼠多发性骨髓瘤数据集的ROC曲线。结果实验组有2025个GOQD-DEG,小鼠多发性骨髓瘤包括594个差异表达基因,两种差异表达基因交集含51个基因。GSEA表明这些交集基因抑制补体和凝血级联通路,下调体液免疫调节或创伤反应过程。Ace、Tcf7l2、Hdc、Lrg1、Cfh、Clu、C3、Serpinb6b、Acss2核心蛋白在小鼠多发性骨髓瘤中高表达,所有核心蛋白的AUC>0.92。结论GOQD刺激的mBMSC与小鼠多发性骨髓瘤包括51个交集基因,这些基因在多发性骨髓瘤中下调补体和凝血级联通路,抑制体液免疫;编码的核心蛋白在多发性骨髓瘤高表达,对多发性骨髓瘤诊断具有重要意义,GOQD刺激的mBMSC可能具有潜在的促进小鼠多发性骨髓瘤发生作用。Objective To explore the effect of graphene oxide quantum dots(GOQD)stimulated mouse bone marrow mesenchymal stem cells(mBMSC)on the occurrence of mouse multiple myeloma,and to analyze the potential molecular mechanism of GOQD-treated mBMSC on multiple myeloma(MM).Methods The normal cultured mBMSC as the control group.The mBMSC cultured with 100μg/ml GOQD as experimental group.After 24 hours of culture at 37℃and 5%CO_(2),transcriptome sequencing technology was used to detect the genes of both groups.By using Edge R package of R4.2.1,the differentially expressed genes(GOQD-DEG)in the experimental group were screened.The mouse myeloma differentially expressed gene(MM-DEG)was obtained by GSE6980 dataset of GEO,and the intersection genes of GOQD-DEG and MM-DEG were subsequently analyzed.Fgsea R package and GO.db R package were used to analyze the biological processes,molecular functions,and KEGG signaling pathways of intersection genes.And Cluster Profiler R package was used for gene set enrichment analysis(GSEA).String was used to construct protein-protein interaction network(PPI)that encoded by intersection genes.Cytohubba v0.1 App was applied to screen the top 10 core proteins.Stats 4.2.1R package and car 3.1-0 R package were used to analyze the expression of core protein in myeloma.pROC 1.18.0R package was used drawing the ROC curve of core proteins in mice multiple myeloma dataset.Results There were 2025 GOQD-DEGs in experimental group.Mice multiple myeloma included 594 differentially expressed genes,and the intersection of the two differentially expressed genes contained 51 genes.GSEA showed that these intersection genes inhibited complement and coagulation cascade pathways and down-regulate humoral immune regulation or wound response processes.The core proteins of Ace,Tcf7l2,Hdc,Lrg1,Cfh,Clu,C3,Serpinb6b and Acss2 were highly expressed in mouse multiple myeloma,and the AUC of all core proteins were greater than 0.92.Conclusions The GOQD stimulated mBMSCs and mouse myeloma contain 51 intersecting genes,these

关 键 词：多发性骨髓瘤 转录组测序技术 氧化石墨烯量子点 小鼠骨髓间充质干细胞 生物信息学 

分 类 号：R73[医药卫生—肿瘤]